To determine if abnormalities in left ventricular function precede angina pectoris and electrocardiographic evidence of myocardial ischemia, we used radionuclide angiocardiography to measure left ventricular ejection fraction, volumes, cardiac output and wall motion in 10 normal subjects and 25 patients with coronary artery disease at rest and during two levels of upright bicylce exercise. In the patients with coronary artery disease, the first radionuclide study during exercise was performed before and the second after the onset of ST-segment depression. In all normal subjects, the ejection fraction increased more than 5%, the end-diastolic volume increased less than 25% and the end-systolic volume decreased from rest to both levels of exercise. Wall motion was normal at rest and increased with exercise. No patient with coronary artery disease had chest pain or ST-segment depression during the first level of exercise. The ejection fraction either decreased or increased less than 5% in 18 patients, the end-diastolic volume increased more than 25% in nine, the end-systolic volume increased in 19 and a segmental contraction abnormality developed in 14. Hemodynamic and wall motion abnormalities occurred in all patients during the second level of exercise when ST-segment depression was present. During exercise in patients with coronary artery disease, abnormalities in left ventricular function frequently develop before angina pectoris and electrocardiographic evidence of myocardial ischemia.